Markus Heinimaa

Prediction of Psychosis in Adolescents and Young Adults at High Risk: Results From the Prospective European Prediction of Psychosis Study

CONTEXT Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. OBJECTIVE To develop a differential predictive clinical model of transition to first-episode psychosis. DESIGN Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. SETTING Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. PARTICIPANTS Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom-based criterion cognitive disturbances (COGDIS). MAIN OUTCOME MEASURE Incidence of transition to psychosis. RESULTS At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. CONCLUSIONS The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

Striatal Dopamine Synthesis in First-degree Relatives of Patients with Schizophrenia

BACKGROUND First degree relatives (FDR) of patients with schizophrenia have higher risk of developing schizophrenia than the general population. Previous positron emission tomography (PET) studies have shown that striatal presynaptic dopamine synthesis capacity is increased in schizophrenia. We investigated whether this same phenomenon is shared by individuals with increased genetic risk for schizophrenia. METHODS We used 6-[18F]-fluorodopa (FDOPA) PET imaging to measure striatal dopamine synthesis capacity. We studied 17 nonpsychotic subjects with an FDR with schizophrenia. This group was compared to 17 healthy subjects with no FDRs with schizophrenia. RESULTS A conventional region of interest (ROI)-analysis indicated that FDOPA uptake (K(i)) in the caudate-putamen was statistically significantly higher in the FDR group than in the control group. A voxel-level analysis confirmed these results. CONCLUSIONS These results suggest that the changes of striatal presynaptic dopamine synthesis seen previously in neuroleptic-naive schizophrenic patients is also present in FDRs of patients with schizophrenia. These findings have implications for the early detection of psychosis as well as for pharmacological interventions in individuals at risk for psychosis.

Disability in people clinically at high risk of psychosis

BACKGROUND Decline in social functioning occurs in individuals who later develop psychosis. AIMS To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. METHOD Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS-II). RESULTS At baseline, the transition group displayed significantly greater difficulties in making new friends (z = -3.40, P = 0.001), maintaining a friendship (z =-3.00, P = 0.003), dealing with people they do not know (z =-2.28, P = 0.023) and joining community activities (z =-2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238-2.550). CONCLUSIONS Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

Axis-I disorders and vulnerability to psychosis

BACKGROUND The psychopathology that manifests during the prodromal phase of first-episode psychosis is varied. Little is known about the clinical diagnoses of subjects with so-called prodromal or psychotic-like symptoms. METHOD Samples of psychotic patients, first-degree relatives (FDRs) of psychotic, or severely ill patients, treatment-seeking patients, and a random community sample (in all 157 subjects) were assessed by the Structured Interview for Prodromal Symptoms (SIPS) and the SCID-I. Vulnerability to psychosis (VTP) was defined by severity of positive symptoms reported in the SIPS interview and associated with lifetime SCID-I diagnoses. RESULTS The number of lifetime diagnoses received increased linearly as the SIPS symptoms approached more psychotic-like phenomena. All VTP subjects received on average 2.5, and currently prodromal subjects 2.9 lifetime SCID-I diagnoses, while the corresponding figure for non-VTP subjects was 0.7 (p<0.0001). Mood disorders and comorbid anxiety disorders were particularly common. CONCLUSION Vulnerability to psychosis seems to be associated with a high number of lifetime Axis-I diagnoses. Occurrence of anxiety disorders is remarkable, and most VTP subjects can be diagnosed with a lifetime mood disorder. VTP subjects require careful assessment of mood and anxiety symptoms and adequate treatment for their multiple disorders.

Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries.

BACKGROUND In selected samples, a considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders. It is not known how clinical diagnoses correspond to or even predict transitions to psychosis (TTP). Our aim was to examine distributions of life-time and current Axis I diagnoses, and their association with TTP in CHR patients. METHODS In the EPOS (European Prediction of Psychosis Study) project, six European outpatient centres in four countries examined 245 young help-seeking patients, who fulfilled the inclusion criteria for clinical risk of psychosis according to the Structured Interview for Prodromal Syndromes (SIPS 3.0) or the Bonn Scale for the Assessment of Basic Symptoms - Prediction List basic symptoms (BASBS-P). Patients who had experienced a psychotic episode lasting more than one week were excluded. Baseline and life-time diagnoses were assessed by the Structured Clinical Interview for DSM-IV (SCID-I). TTP was defined by continuation of BLIPS for more than seven days and predicted in Cox-regression analysis. RESULTS Altogether, 71% of the CHR patients had one or more life-time and 62% one or more current SCID-I diagnosis; about a half in each category received a diagnosis of life-time depressive and anxiety disorder. Currently, 34% suffered from depressive and 39% from anxiety disorder. Four percent received a current SCID diagnosis of bipolar, and 6.5% of somatoform disorder. During follow-up, 37 (15.1%) patients had developed full-blown psychosis. In bivariate analyses, current non-psychotic bipolar disorder associated significantly with TTP. In multivariate analyses, current bipolar disorder, somatoform and unipolar depressive disorders associated positively, and anxiety disorders negatively, with TTP. CONCLUSIONS Both life-time and current mood and anxiety disorders are highly prevalent among clinical help-seeking CHR patients and need to be carefully evaluated. Among CHR patients, occurrence of bipolar, somatoform and depressive disorders seems to predict TTP, while occurrence of anxiety disorder may predict non-transition to psychosis.

Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis

Dragt S, Nieman DH, Schultze‐Lutter F, van der Meer F, Becker H, de Haan L, Dingemans PM, Birchwood M, Patterson P, Salokangas RKR, Heinimaa M, Heinz A, Juckel G, Graf von Reventlow H, French P, Stevens H, Ruhrmann S, Klosterkötter J, Linszen DH, on behalf of the EPOS group. Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis.

Association of cannabis use with prodromal symptoms of psychosis in adolescence

Recent interest has focused on the association between cannabis use and risk of psychosis. In the largest unselected, population-based study on this topic to date, we examined cannabis use and prodromal symptoms of psychosis at age 15-16 years among 6330 adolescents. Those who had tried cannabis (n=352; 5.6% of the total sample) were more likely to present three or more prodromal symptoms even after controlling for confounders including previous behavioural symptoms (OR=2.23; 95% CI 1.70-2.94). A dose-response effect was seen. We conclude that cannabis use is associated with prodromal symptoms of psychosis in adolescence.

Prediction of psychosis in clinical high-risk patients by the Schizotypal Personality Questionnaire. Results of the EPOS project

OBJECTIVE Schizotypal features indicate proneness to psychosis in the general population. It is also possible that they increase transition to psychosis (TTP) among clinical high-risk patients (CHR). Our aim was to investigate whether schizotypal features predict TTP in CHR patients. METHODS In the EPOS (European Prediction of Psychosis Study) project, 245 young help-seeking CHR patients were prospectively followed for 18 months and their TTP was identified. At baseline, subjects were assessed with the Schizotypal Personality Questionnaire (SPQ). Associations between SPQ items and its subscales with the TTP were analysed in Cox regression analysis. RESULTS The SPQ subscales and items describing ideas of reference and lack of close interpersonal relationships were found to correlate significantly with TTP. The co-occurrence of these features doubled the risk of TTP. CONCLUSIONS Presence of ideas of reference and lack of close interpersonal relations increase the risk of full-blown psychosis among CHR patients. This co-occurrence makes the risk of psychosis very high.

The Strauss and Carpenter Prognostic Scale in subjects clinically at high risk of psychosis

Objective:  To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis.

Pathways to care in subjects at high risk for psychotic disorders — A European perspective ☆

Evidence-based decisions on indicated prevention in early psychosis require large-scale studies on the pathways to care in high-risk subjects. EPOS (The European Prediction of Psychosis Study), a prospective multi-center, naturalistic field study in four European countries (Finland, Germany, The Netherlands and England), was designed to acquire accurate knowledge about pathways to care and delay in obtaining specialized high risk care. Our high risk sample (n=233) reported on average 2.9 help-seeking contacts, with an average delay between onset of relevant problems to initial help-seeking contact of 72.6 weeks, and between initial help-seeking contact and reaching specialized high risk care of 110.9 weeks. This resulted in a total estimated duration of an unrecognized risk for psychosis of 3 ½ years. Across EPOS EU regions, about 90% of care pathway contacts were within professional health care sectors. Between EPOS regions, differences in the pathways parameters including early detection and health-care systems were often very pronounced. High-risk participants who later made transition to a full psychotic disorder had significantly longer delays between initial help-seeking and receiving appropriate interventions. Our study underlines the need for regionally adapted implementation of early detection and intervention programs within respective mental health and health care networks, including enhancing public awareness of early psychosis.